The studies in this application are designed to better understand the regulation of body fat mass and the mechanisms determining body fat distribution in humans. Three Specific Aims are proposed: 1. To determine whether experimentally-induced or spontaneous variations in plasma leptin levels predict subsequent changes in body composition. The protocols employed will also elucidate the mechanism by which high carbohydrate diets induce satiety and weight loss, and the mechanism of involuntary weight loss in the elderly. 2. To examine the relationships among central body fat redistribution, changes in adipogenic gene expression, and atherogenic changes in plasma lipids and insulin sensitivity. The model for this work will be the body fat redistribution that occurs in subjects receiving aggressive antiretroviral therapy for HIV infection. 3. To determine whether changes in uncoupling protein (UCP) gene expression act to attenuate diet-induced changes in body fat mass. This study will use the technology developed for Specific Aim 2 to ascertain whether muscle and fat UCP expression change in parallel with energy expenditure following experimental weight gain and weight loss in human subjects. The applicant has successfully trained several young physician investigators in patient-oriented and basic research, and a plan to continue doing so is presented.